FDA Delays Approval of Xarelto Antidote

As the number of lawsuits against Xarelto manufacturer Bayer approaches 7,000, the company has received more bad news: FDA approval for the much-anticipated antidote, under development by a small California-based biotech firm, has been delayed.

Xarelto (rivaroxaban) is one of the “new generation” of anticoagulant medications that have been developed over the past several years as a replacement for warfarin, the standard treatment for over six decades. Anticoagulants are often mistakenly labeled as “blood thinners;” in actuality, these medications inhibit blood clotting. They are typically prescribed for patients at risk of stroke or cardiac arrest due to the formation of blood clots.

Xarelto operates by preventing the liver from producing a biochemical substance known as “Factor Xa” (10-A), which is crucial to the clotting process. Xarelto has been touted as easier to administer as opposed to warfarin, since there are fewer drug interactions and dietary restrictions. The problem – and the cause of action in the growing number of lawsuits – is that once Xarelto is in the patient’s system, the slightest bump can lead to uncontrolled and potentially fatal bleeding. Unlike warfarin (a form of rat poison), there is no reversal agent.

Last year, Portola Pharmaceuticals, a small company in the San Francisco Bay area, was busy at work on an antidote, AndexXa (andexanet alfa). The medication was developed from recombinant human DNA, designed to prevent Factor Xa inhibitors such as Xarelto from doing its job. AndexXa is essentially a “decoy” that targets Xarelto, literally tricking it into binding with itself rather than the patient’s own natural Factor Xa. This way, the patient’s own clotting mechanism would be restored and the bleeding stopped. Phase 3 studies were completed last fall and the results published in the November 2015 edition of the New England Journal of Medicine.

This summer, Portola filed an application with the Food and Drug Administration for a biologics license for its new medication. In that application, Portola listed other new generation anticoagulants for which the antidote would be effective. These included Lovenox, Xaparin and Clexane (enoxoparin), Savasaya (edoxaban) and Eliquis (apixaban). Therein lies the problem for the FDA. In its rejection of Portola’s application, the federal regulatory agency requested additional information supporting Portola’s inclusion of the latter medications in its labeling as well as more data on the manufacturing process.

The FDA’s initial rejection of AndexXa comes as a surprise – and bad news for the some 100,000 patients per year who suffer from uncontrolled hemorrhaging as a result of using Factor Xa inhibitors. Part of the problem is that Portola was in a hurry to get the drug approved and on to the market, and requested an accelerated review of its application. In its rejection letter, the FDA expressed concerns about the manufacturing process as well as the effectiveness of AndexXa on anticoagulants other than rivaroxaban and apixaban.

It’s not necessarily over for the drug that promises to be an antidote for hemorrhaging caused by Xarelto and Eliquis. Portola may have to remove enoxoparin and edoxaban from the label, and in any case will need to provide greater detail about the clinical studies and production. The bottom line for now is that patients will have to wait another six months to a year before a reliable antidote for new generation anticoagulants is available.

K.J. McElrath is a former history and social studies teacher who has long maintained a keen interest in legal and social issues. In addition to writing for The Ring of Fire, he is the author of two published novels: Tamanous Cooley, a darkly comic environmental twist on Dante's Inferno, and The Missionary's Wife, a story of the conflict between human nature and fundamentalist religious dogma. When not engaged in journalistic or literary pursuits, K.J. works as an entertainer and film composer.

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